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| Ultrasensitive Detection of miRNA Based on a Biofunctionalized Mesoporous Silica Nanomaterial |
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| DOI： |
| KeyWord:mesoporous silica nanoparticles cyclic amplification controlled release miRNA |
| Author | Institution |
| LI Jing-jing,WU Dan,OUYANG Jin,NA Na |
Key Laboratory of Radiopharmaceuticals，College of Chemistry，Beijing Normal University， Beijing ，China |
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| Abstract: |
| Nanomaterials have exhibited great potentials in the field of biological diagnosis and treatment．Recently，the design of an ideal drug delivery system with targeted recognition and controlled release，especially triggered by exclusive endogenous stimulus，has obtained great attentions．Meanwhile，silica based nanomaterials have attracted tremendous attention in biomedical applications in the past decades due to their superior biocompatibility and controllable structures．Developing a silica based nanoparticles mediated drug delivery system for transporting therapeutics to targeted sites and releasing them on demand has been one of most exciting research topics．Herein，the silica nanoparticles were selected for the construction based on the mesoporous silica nanoparticles’ advantages such as good biosafety and easy regulations on morphology，size，specific surface area，tunable pore sizes and easy functionalization．In addition，the surface of the material is easily functionalized due to the presence of silanol groups on the surface，which further improves the therapeutic effect of drugs and reduces the side effects．In this work，an aptamer-targeted silicon nanomaterial was constructed as a carrier for intracellular reagent delivery，ultra-sensitive detection of miRNA and controlled drug releases．Mesoporous silica nanoparticles（MSNs） at 55 nm were firstly prepared for the following functionalization and loadings by traditional st?ber method．Thereafter，the hollow structure of MSNs was loaded with the anticancer drug doxorubicin（Dox）．In addition，the hairpin G－quadruplex DNA（HG1，HG2） was modified on the MSNs by electrostatic action to form a DNA gate to prevent the leaking of Dox．Therefore，in the tumor cells with the presence of miRNA－21 target，the cyclic amplification was triggered with HG1 and HG2．HG1 was employed to recognize and hybridize with miRNA－21，producing a single stranded tail in HG1，which dissociated and increased the mobility of HG1 on MSNs，facilitating its hybridization with HG2．HG2 met unfolded HG1 and initiated hairpin assembly，yielding double strand G－quadruplex（dsG） DNA to result in the signal amplification for the sensitive target detections．In this process，miRNA－21 could also serve as an exclusive key to release Dox by competing against DNA on surface of MSNs．This was achieved by the fully hybridization of miRNA－21 with HG1 and HG2 on MSNs surface，which thereby triggered on-command release of Dox from Dox@MSNs－DNA．As a result，the limit of the detection was 0.04 nmol/L for miRNA－21 detection．Therefore，maximum therapeutic efficacy and minimum side effects were achieved by virtue of the aptamer-targeted delivery and miRNA-targeted drug release．Endowed with highly specific and sensitive detection and controllable release of drugs，this multifunctional nanomaterial show a certain potential in diagnosis and treatment. |
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